UMIN-CTR Clinical Trial

Public title

Multicenter study of a randomized controlled trial with or without maintenance/intensification therapy in patients with previously untreated acute promyelocytic leukemia (JALSG APL97 study)

Acronym

Randomized trial with or without maintenance/intensification therapy in patients with acute promyelocytic leukemia (JALSG APL97 study)

Scientific Title

Multicenter study of a randomized controlled trial with or without maintenance/intensification therapy in patients with previously untreated acute promyelocytic leukemia (JALSG APL97 study)

Scientific Title:Acronym

Randomized trial with or without maintenance/intensification therapy in patients with acute promyelocytic leukemia (JALSG APL97 study)

Region

Japan

Condition

acute promyelocytic leukemia (APL)

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Differentiation therapy of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) followed by intensive chemotherapy has shown significant improvement of event-free survival in patients with APL. After consolidation therapy, the maintenance/intensification therapy has been given based on the previous results of the Japan Adult leukemia Study Group (JALSG) AML87 study, in which patients receiving the longer maintenance/intensification therapy showed significantly better relapse-free survival (RFS). If short-term treatment without maintenance/intensification therapy shows identical RFS rates as compared with long-term therapy, it would be of benefit to quality of life in the patients and medical costs. With this concern, the JALSG has planned a prospective randomized controlled trial comparing observation and 6 courses of maintenance/intensification therapy for APL patients who are negative PML-RARa at the end of 3 courses of consolidation therapy.

Basic objectives2

Bio-equivalence

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Phase III

Primary outcomes

relapse-free survival at 5 years

Key secondary outcomes

overall survival at 5 years, complete remission rate, event-free survival at 5 years, efficacy of detection of PML-RARalpha

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

No treatment

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

6 courses of maintenance/intencification therapy consisting of enocitabine, daunorubicin, mercaptopurine, mitoxantrone, etoposide, vindesine, and aclarubicin

Interventions/Control_2

no maintenance/intensification therapy

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

15

years-old

<=

Age-upper limit

70

years-old

>=

Gender

Male and Female

Key inclusion criteria

1. Previously untreated APL
2. Age between 15 and 70 years
3. Performance status between 0 and 3 (ECOG criteria)
4. Adequate functioning of the liver (serum bilirubin level < 2.0 mg/dL), kidneys (serum creatinine level < 2.0 mg/dL), lung (PaO2 > 60 mmHg or SpO2 > 93%) and heart (no severe abnormalities detected on electrocardiograms)
5. Written informed consent to participate the trial

Key exclusion criteria

1. Uncontrolled active infection
2. Past history of myocardial infarction or cardiac failure
3. Past history of renal failure
4. Uncontrolled diabetes mellitus
5. Liver cirrhosis
6. Leukemic involvement in the CNS
7. Another severe and/or life threatening disease
8. Pregnant and/or lactating woman
9. Positive for HIV antibody test

Target sample size

234

Name of lead principal investigator

1st name
Middle name
Last name	Ryuzo Ohno

Organization

Aichi Cancer Center

Division name

Honor Director

Zip code

Address

1-1 Kakodono, Chigusa, Nagoya 464-8681, Japan

TEL

052-762-6111

Email

Name of contact person

1st name
Middle name
Last name	Norio Asou

Organization

Kumamoto University School of Medicine

Division name

Department of Hematology

Zip code

Address

1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan

TEL

096-373-5156

Homepage URL

Email

ktcnasou@gpo.kumamoto-u.ac.jp

Institute

Japan Adult Leukemia Study Group

Institute

Department

Personal name

Organization

Ministry of Health, Labor and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

日本大学医学部血液膠原病内科、東京都立駒込病院内科・血液内科、名古屋大学医学部第一内科、岡崎市民病院内科、大同病院、豊橋市民病院血液内科、一宮市立市民病院、名古屋大学医学部難治感染症部、愛知県がんセンター血液化学療法部、名古屋第一赤十字病院内科、藤田保健衛生大学医学部内科、三重大学医学部血液内科、三重厚生連鈴鹿中央総合病院、鈴鹿回生総合病院内科、松坂市民病院、山田赤十字病院、武内病院、近畿大学医学部血液・腎臓・膠原病内科、大阪府立成人病センター第五内科、長崎大学医学部原研内科、佐世保市立総合病院、熊本大学医学部第二内科、ＮＴＴ西日本九州病院血液免疫内科、自治医科大学血液学、国立療養所南岡山病院、国立病院岡山医療センター、公立学校共済組合中国中央病院、群馬大学医学部第三内科、群馬県立がんセンター血液内科、国立療養所西群馬病院、公立藤岡総合病院、福井大学医学部第一内科、倉敷中央病院、国立がんセンター、埼玉医科大学第一内科、兵庫医科大学第二内科、国立大阪病院、川崎医科大学血液内科、高知県・高知市病院企業団立高地医療センター、千葉大学医学部第二内科、千葉市立青葉病院内科、奈良県立医科大学呼吸器感染症血液内科、東京慈恵会医科大学血液・腫瘍内科、獨協医科大学血液内科、国立名古屋病院血液センター、亀田総合血液腫瘍内科、太田西ノ内病院血液疾患センター、高知大学医学部血液・呼吸器内科、滋賀医科大学第二内科、社会保険滋賀病院内科、国立がんセンター東病院内科、安城更生病院、聖マリアンナ医科大学血液腫瘍内科、聖マリアンナ医科大学横浜西部病院血液腫瘍内科、京都府立医科大学医科大学第二内科、公立南丹病院内科、信州大学医学部第二内科、東京女子医科大学血液内科、浜松医科大学第三内科、焼津市立総合病院、浜松医療センター血液科、袋井市立袋井市民病院内科、鹿児島大学第一内科、今村病院本院、栃木県立がんセンター、金沢大学医学部第三内科、東京医科大学第一内科、杏林大学医学部第二内科、北海道大学医学部血液内科、函館中央病院、関西医科大学第一内科、済生会前橋病院血液内科、東海大学医学部血液リウマチ内科、海老名総合病院、山口大学医学部第三内科、山口県立中央病院、若弘会病院、大阪大学医学部第三内科、日生病院第三内科、東京大学医学部血液腫瘍内科、新潟大学医学部第一内科、大分県立病院血液内科、国立病院九州がんセンター造血器科、帝京大学医学部内科、帝京大学医学部附属市原病院、愛知医科大学第二内科、北里大学医学部第三内科（東京都立墨東病院）、山形大学医学部第三内科、札幌北楡病院内科、青森県立中央病院リウマチ血液内科、兵庫県立成人病センター血液内科、京都府立医科大学第三内科、大阪市立総合医療センター、防衛医科大学校第三内科、秋田大学医学部第三内科

Date of disclosure of the study information

2005

Year

09

Month

14

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

http://www.jalsg.jp/04/02.html

Number of participants that the trial has enrolled

Results

1) Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission (CR).
2) A total of 175 patients negative for PML-RARalpha at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n = 89) or observation (n = 86).
3) Predicted 6-year DFS was 79.8% for the observation group and 63.1% for the
chemotherapy group, showing no statistically significant difference between the two groups (P = 0.20).
4) Predicted 6-year survival of patients assigned to the observation was
98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P = 0.014).

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

1997

Year

04

Month

12

Day

Date of IRB

Anticipated trial start date

1997

Year

05

Month

01

Day

Last follow-up date

2008

Year

06

Month

01

Day

Date of closure to data entry

2009

Year

06

Month

01

Day

Date trial data considered complete

2009

Year

12

Month

01

Day

Date analysis concluded

2012

Year

12

Month

01

Day

Other related information

1. Asou N, Kishimoto Y, Kiyoi H, Okada M, Kawai Y, Tsuzuki M, Horikawa K, Matsuda M, Shinagawa K, Kobayashi T, Ohtake S, Nishimura M, Takahashi M, Yagasaki F, Takeshita A, Kimura Y, Iwanaga M, Naoe T, Ohno R. A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RARalpha transcript after consolidation therapy: The Japan Adult Leukemia Study Group (JALSG) APL97 study. Blood 2007;110:59-66.

2. Yanada M, Matsushita T, Asou N, Kishimoto Y, Tsuzuki M, Maeda Y, Horikawa K, Okada M, Ohtake S, Yagasaki F, Matsumoto T, Kimura Y, Shinagawa K, Iwanaga M, Miyazaki Y, Ohno R, Naoe T. Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome. Eur J Haematol. 2007;78(3):213-219.

3. Ono T, Takeshita A, Iwanaga M, Asou N, Naoe T, Ohno R; Japan Adult Leukemia Study Group. Impact of additional chromosomal abnormalities in patients with acute promyelocytic leukemia: 10-year results of the Japan Adult Leukemia Study Group APL97 study. Haematologica. 2011;96(1):174-176.

4.Ono T, Takeshita A, Kishimoto Y, Kiyoi H, Okada M, Yamauchi T, Tsuzuki M, Horikawa K, Matsuda M, Shinagawa K, Monma F, Ohtake S, Nakaseko C, Takahashi M, Kimura Y, Iwanaga M, Asou N, Naoe T; the Japan Adult Leukemia Study Group. Long-term outcome and prognostic factors of elderly patients with acute promyelocytic leukemia. Cancer Sci 2012;103:1974-1978.

Registered date

2005

Year

09

Month

13

Day

Last modified on

2012

Year

12

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000250